Abstract
In order to study the activation of suppressor T lymphocytes by thyroid-specific antigens in autoimmune thyroid disease (AITD), we have investigated the effects of the organ-specific antigens, thyroperoxidase (TPO), thyroglobulin (Tg), and thyroid microsomal antigen (TMc), as well as renal microsomes (RMc) as a control antigen, on the activation of suppressor T lymphocytes; this was accomplished by measuring major histocompatibility complex class II (HLA-DR) expression on their surfaces by flow cytometric analysis. Peripheral blood mononuclear cells (PBMC), obtained from 33 patients with Graves’ disease (GD), 26 with Hashimoto’s thyroiditis (HT), 5 with nontoxic nodular goiter (NTG), and 30 normal persons (N), were cultured for 7 days in the presence or absence of TPO, Tg, or RMc at final concentration of 10, 100, and 1000 ng/ml. Cultured cells were stained with fluorescent-conjugated monoclonal antibodies (anti-CD8, anti-CD11b, and anti-HLA-DR), and the activation of CD8+ and CD8+CD11b+ (pure suppressor) T cells by the antigens was analyzed on a flow cytometer. In the absence of antigen, i.e., the autologous mixed lymphocyte reaction (AMLR), CD8+ and CD8+CD11b+ T lymphocytes from patients with GD and HT showed significantly lower activation as compared to N. We measured the Stimulation Index (SI) of activated T lymphocytes to compare antigen-specific activation between CD8+ and CD8+CD11 b+ cells from normal persons and patients. With stimulation of 100 and/or 1000 ng/mL of TPO or Tg, SI of activated CD8+ cells was significantly (p<0.05 to 0.01) lower in GD and HT as compared with N. Furthermore, when results with CD8+CD11b+ (pure suppressor) T lymphocytes were analyzed, this became even more significant (p<0.001). The SI of activated CD8+ and CD8+CD11b + T lymphocytes correlated significantly (r= 0.86, p<0.02). On the other hand, both normal and patients’ suppressor T lymphocytes were activated equally by RMc antigens. In conclusion: i) Impaired AMLR reactivity of suppressor T lymphocytes was observed in GD and HT patients; ii) Activation of AITD suppressor T lymphocytes was significantly reduced by thyroid-specific antigens but not control antigen, and iii) There thus appears to be a defect in specific antigen induction of support T lymphocytes which may be important in the pathogenesis of AITD.
Original language | English (US) |
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Pages (from-to) | 609-617 |
Number of pages | 9 |
Journal | Journal of Endocrinological Investigation |
Volume | 16 |
Issue number | 8 |
DOIs | |
State | Published - Sep 1993 |
Externally published | Yes |
Keywords
- Suppressor T lymphocytes
- TPO
- autoimmune thyroid disease
- flow cytometry
- thyroglobulin
- thyroid-specific antigen
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology